Hauptmann G, Tappeiner G, Schifferli J A
Laboratoire de Recherches en Immunologie, Strasbourg, France.
Immunodefic Rev. 1988;1(1):3-22.
The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes, C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, and is also remarkable by the high frequency of the null alleles, C4AQ0 and C4BQ0. Despite considerable structural homology, the gene products of the two loci differ in hemolytic activities, antigenic reactivities and covalent binding affinities to antigens and antibodies. Complete C4 deficiency is exceptional because this condition appears only in homozygotes for the very rare double-null haplotype C4AQ0,BQ0. In contrast, partial C4 deficiency is a common immune protein defect in all human populations as a consequence of the high frequency of the C4 half-null haplotypes. Complete C4 deficiency in most cases gives rise to SLE and an increased susceptibility to infections, and partial C4 deficiencies predispose to different auto-immune diseases related to extended HLA haplotypes bearing the C4 half-null haplotypes. Studies at the DNA level have shown that about half of the null alleles are due to deletions involving C4A and 21-OHA, C4B and 21-OHA or C4B and 21-OHB. Larger deletions including both C4A and C4B genes have never been observed. Partial C4 deficiency may be observed in combination with other complement deficiencies or immune defects, and allo- or auto-anti-C4 immunization is also a possible consequence of this genetic abnormality. Although the pathogenesis of the diseases related to complete and partial C4 deficiencies is not yet clearly understood, it is evident that C4 null alleles represent interesting markers and additive risk factors for autoimmune phenomena.
人类补体的高度多态性第四成分（C4）通常由两个基因C4A和C4B编码，这两个基因与21-羟化酶（21-OH）基因相邻，并且其无效等位基因C4AQ0和C4BQ0的频率也很高，十分引人注目。尽管两个基因座的基因产物在结构上有相当高的同源性，但它们在溶血活性、抗原反应性以及与抗原和抗体的共价结合亲和力方面存在差异。完全C4缺乏症很罕见，因为这种情况仅出现在非常罕见的双无效单倍型C4AQ0,BQ0的纯合子中。相比之下，部分C4缺乏是所有人群中常见的免疫蛋白缺陷，这是由于C4半无效单倍型的高频率所致。大多数情况下，完全C4缺乏会导致系统性红斑狼疮（SLE）并增加感染易感性，而部分C4缺乏则易引发与携带C4半无效单倍型的扩展HLA单倍型相关的不同自身免疫性疾病。DNA水平的研究表明，约一半的无效等位基因是由于涉及C4A和21-OHA、C4B和21-OHA或C4B和21-OHB的缺失。从未观察到包括C4A和C4B基因在内的更大缺失。部分C4缺乏可能与其他补体缺乏或免疫缺陷同时出现，同种或自身抗C4免疫也是这种遗传异常的一个可能后果。尽管与完全和部分C4缺乏相关疾病的发病机制尚未完全清楚，但很明显，C4无效等位基因是自身免疫现象的有趣标志物和附加风险因素。
